Andrew Wells, PhD

Dr. Andrew Wells is an Associate Professor of Pathology and Laboratory Medicine. His research is focused on fundamental questions of how immune tolerance is achieved and maintained in healthy individuals, and how it breaks down in autoimmunity and organ transplant rejection. Early work in his laboratory pioneered the concept that stable immunological tolerance is achieved through epigenetic imprinting and gene silencing in T cells. His lab showed that transcriptional factors like Ikaros and Foxp3 cooperate with DNA methyltransferases and chromatin modifying complexes to regulate inflammatory genes and control T cell immune responses. They also showed that the cyclin-dependent kinase pathway is dispensable for T cell proliferation, but has unexpected roles in T cell differentiation and tolerance. More recently my research has transitioned from mouse to human, and from the focus on one molecule or gene at a time to exploring mechanisms of immune tolerance at genome scale. This transition leveraged new advances in genome sequencing technology, and involved adopting multi-omic approaches such as ChIP-seq, ATAC-seq, RNA-seq, Capture-C, HiC, CRISPR-CAS9, bioinformatics, and systems biology analysis. They have also leveraged genome-wide association studies (GWAS) of autoimmunity to explore the impact of disease-associated human genetic variation on transcription factor occupancy, histone modification, and long-range interactions between cis-regulatory elements and gene promoters in immune cells. A major current effort in the laboratory is the focus on potentially novel immunomodulatory drug targets implicated by our multi-omic studies in inflammatory disease, organ transplant rejection, and cancer.